Current gene therapy regimens used for treatment of cancer has many limitations, including lack of tissue-specificity, borderline efficacy, and inadequate delivery methods. Most attempts to optimize gene therapy have focused on delivery of the recombinant therapeutic gene to the target tumor and restricted expression of the therapeutic gene in the target tumor. Another limitation is the lack of reliable and non-invasive methods for detecting and monitoring delivery and expression of the therapeutic gene.
One strategy for optimizing gene therapy methods includes the two-component reporter gene system, or the so-called two-step transcription amplification system (Segawa, et al., 1998 Cancer Res. 58:2282-2287). In this system, the first step involves a tissue-specific or tumor-specific promoter to drive expression of a transcription activator. In the second step, the transcription activator induces expression of a reporter or therapeutic gene product.